Cyclophosphamide (CY) is a highly active and widely used anti-neoplastic agent in animals and man. The administration of CY at high doses which are therapeutic for neoplasia, however, causes a generalized immunosuppression of both cellular and humoral immunity. The overall objective of this proposal is to focus on the cellular immune arm of the immune response with specific emphasis on rescuing the cytotoxic T-lymphocyte (CTL) response after the administration of CY. These studies will include the use of allogeneic and syngeneic tumors and CY-resistant tumor cell lines. The restoration of CTL activity, after CY administration, will be accomplished by the use of helper cells and T-cell derived helper factors. Optimal regimens for the dose, timing and delivery of either helper cells or their factors will be determined. The recovery of CTL activity by helper cell or helper factor administration, after CY therapy, will be used as a prerequisite for establishing tumor therapy protocols. The tumor systems to be employed will be the following transplantable tumors: L1210 in syngeneic DBA/2 mice; AKSL leukemic cells in syngeneic AKR mice and the CD8Fl transplantable mammary tumor cell line in syngeneic CD8Fl mice. Future experiments will include the use of spontaneous tumor models in which after diagnosis and staging the tumor bearing mice will be injected with therapeutic doses of CY followed by an optimal regimen of helper factor administration in vivo. Cures, reduction in tumor volume, and mean survival times will be determined.